Role of the Testosterone in ‎memory impairment of Alzheimer ‎disease induced with streptozoocin ‎in mature male Rats

Alzheimer's disease is a common form of progressive dementia and usually occurs between the sixth and ninth decades of life, given that there is a direct relationship between steroid hormones and neurodegenerative diseases, so the present study was designed to explore effect of testosterone in memory impairment induced by intra-cerebroventricular (icv) injection of streptozptocin (STZ) as a model of sporadic Alzheimer disease (AD). Study was carried out on male Wistar rats. Adult male Wistar rats were intracerebroventricularly (icv) infused with STZ (3mg/kg/icv) on d 1 and d 3, and a passive avoidance task was assessed 2 weeks after the first injection of STZ. Castration surgery was performed in another group of rats, and the passive avoidance task was assessed 4 weeks after the operation. Testosterone (1 mg/kg.d, SC), the androgen receptor antagonist flutamide (10 mg/kg.d, ip), the estrogen receptor antagonist tamoxifen (1 mg/kg.d, ip) or the aromatase inhibitor letrozole (4 mg/kg.d, ip) were administered for 6 d after the first injection of STZ.  STZ administration and castration markedly decreased both STL1 (the short memory) and STL2 (the long memory) in passive avoidance tests. Testosterone replacement almost restored the STL1 and STL2 in castrated rats, and significantly prolonged the STL1 and STL2 in STZ-treated rats. Administration of flutamide, letrozole or tamoxifen significantly impaired the memory in intact rats, and significantly attenuated the testosterone replacement in improving STZ- and castration-induced memory impairment. Testosterone administration ameliorates STZ- and castration-induced memory impairment in male Wistar rats.